The objectives of these studies are to establish the biochemical basis for the pathogenesis of cleft palate in mice by the mycotoxin, secalonic acid D (SAD); and to confirm the(se) mechanism(s) by demonstrating a reversal of such biochemical effects(s) by the antiteratogenic agent, dimethylsulfoxide (DMSO). Timed-pregnant CD-l mice will be exposed to 30 mg/kg of SAD, intraperitoneally, in 5% (w/v) sodium bicarbonate (SB) or a 20% solution of DMSO in SB. Fetal palates collected between days 13.5 and 15.5 of development will be subjected to: 1) mitochondrial isolation to study palatal cellular respiration using an oxygen electrode, 2) isolation of plasma membranes to assess total and quabain sensitive (Na -K+) ATP-ase activities, 3) quantitation of palatal adenosine triphosphate and guanosine triphosphate levels using high performance ion-pai chromatography, 4) measurement of membrane phospholipase A2 activity using release of (1-14C) oleic acid from exogenous (1-14C) dioleoylphosphatidylcholine by palate homogenates, 5) assay of cyclooxygenase pathway enzyme activity by monitoring the conversion of exogenous C-arachidonic acid by palatal slices and homogenates into prostaglandins, 6) adenylate and guanylate cyclase assay of tissue homogenates, and 7) measurement of phosphodiesterase activity in palatal homogenates. These studies test the hypotheses that SAD-induced alterations in palatal cellular energy metabolism, prostaglandin synthesis, cyclase (adenylate and guanylate) activities, and/or phosphodiesterase activity could lead to previously observed changes in palatal cyclic nucleotide patterns and ultimately cleft palate by SAD, and that DMSO prevents the teratogenic effect of SAD by normalizing these SAD-induced changes. The results of these studies would not only indicate, in vivo, the relative importance of mechanisms (for e.g., prostaglandin synthesis) previously shown to be affected in vitro by other teratogens but also establish certain new biochemical events of normal palatogenesis (for e.g. guanylate cyclase and cGMP-phosphodiesterase) and indicate the importance of all of these pathways in SAD-induced cleft palate. This would lead to a greater understanding of the pathogenesis of environmentally caused cleft palate and may suggest preventive approaches to this common human malformation.